Migration of arterial smooth muscle cells (SMC) into the intimal layer of blood vessel walls is a key event in the development of atherosclerotic lesions and also of restenosis after coronary balloon angioplasty. A number of SMC migration factors secreted by vascular cells or derived from other blood components have been identified. These migration factors include platelet-derived growth factor, interleukin-1, transforming growth factor-.beta., fibronectin, vitronectin, fibrinogen and oxidized low density lipoprotein.
Smooth muscle cell-derived migration factors (SDMF) from rat and rabbit have been described by Koyama et al. in Atherosclerosis 86, 219-226 (1991). Subsequent purification and biochemical and pharamacological studies of the rat SDMF protein from aortic SMC were reported by the same group in Koyama et al., J. Biol. Chem. 268, 13301-13308 (1993).
The studies indicated that rat SDMF is a potent SMC migration factor which does not enhance proliferation of SMC. The 58 kDa SMC-secreted protein differed biochemically from other know SMC migration factors and was reported to induce migration by an autocrine mechanism. Sequencing and/or cloning of the rat SDMF was not reported.
SMC migration is involved in a number of blood vessel pathologies. As a SMC autocrine migratory factor, SDMF is thought to play an important role in blood vessel pathology, e.g., the formation of intimal thickening of atherosclerotic lesions. The involvement of SDMF in the regulation of SMC migration necessitates the full identification of SDMF and its cDNA. A need also exists for compounds which modulate the activity of SDMF, for methods to identify such modulators and for reagents useful in such methods.